Antimicrobial hand wash

ABSTRACT

An antimicrobial hand wash includes a soap, an antimicrobial agent, and an amine salt. The amine salt is found to increase the antimicrobial efficacy of the hand wash. The amine salt produced through the reaction of monoethanolamine and lactic acid is of particular interest as a soap addition. In processes of this invention, it is possible to create the desired amine salt in the soap in situ.

CROSS REFERENCE TO RELATED APPLICATION

This is a divisional application of application Ser. No. 11/494,473filed Jul. 27, 2006, which is incorporated herein by reference.

TECHNICAL FIELD

The present invention generally relates to antimicrobial compositions,and, more particularly, relates to soaps that include an efficacyboosting chemical derived from the neutralization of a nitrogeneous basewith a neutralizing acid.

BACKGROUND OF THE INVENTION

True soaps are created through a saponification reaction in which fats,more appropriately, fatty acids, are neutralized with a base. To ensurethat the reaction is driven to completion, it is common practice toemploy an excess of base. Because soaps are generally compatible withantimicrobial agents, they are often used in liquid antimicrobial handwashes. Such soap-based antimicrobial hand washes are found in numerousmarkets including healthcare, food services, and consumer.

Antimicrobial agents are selected from a variety of classes, includingbisguanidine (e.g., chlorhexidine digluconate), diphenyl compounds,benzyl alcohols, trihalocarbanilides, quaternary ammonium compounds,ethoxylated phenols, and phenolic compounds, such as halo-substitutedphenolic compounds, like p-chloro-m-xylenol (known as “pcmx”) and2,4,4′-trichloro-2′hydroxy-diphenylether (known as “triclosan”).Although these antimicrobial agents are used in numerous hand washformulations, they are not without some detrimental properties.Antimicrobial agents are typically irritating to the skin. And whileskin irritancy is a concern for any cosmetic or drug formulation, it iseven more pertinent to hand washes because of the sensitivity of thebody areas treated. There is a need to minimize the amount ofantimicrobial agent present in a hand wash formulation, in order tominimize the irritancy thereof. But by reducing the amount ofantibacterial agent present, it is expected that the antimicrobialproperties of the hand wash will also be reduced, and, thus, there existcompeting desires to reduce antimicrobial agents while maintainingantimicrobial efficacy.

Another important concern for a wash formulation is the aesthetics ofthe product. For example, the public has come to associated foamingability with cleaning ability, and, as a result, consumers are lesslikely to purchase a wash formulation that does not foam while washing.This consumer perception drives those in the market to formulate washingproducts which produce copious amounts of foam. As mentioned above,irritancy is a concern. The color and odor of a wash formulation is alsoimportant. When soaps are used in conjunction with antimicrobial agents,they do not present the best of each of these desired properties.Although the presence of the soap allows for a reduction in the amountof antimicrobial agent while maintaining a relatively high log kill,antimicrobial soap products tend to irritate the skin. Thusly, skinconditioning agents need added to produce an aesthetically pleasing handwash.

SUMMARY OF THE INVENTION

This invention involves the creation of a soap through a saponificationreaction and the creation of an amine salt for inclusion in the soap.Herein, “primary” relates to those acids and bases employed in thesaponification reaction, while “secondary” relates to those acids andbases employed to create the amine salt, although, when a nitrogenousbase is employed, it can serve as both the primary and the secondarybase. “Nitrogenous base” refers to bases that include at least onenitrogen bound to no more than three substituents.

In one embodiment, this invention provides an antimicrobial hand washcomprising a soap and the reaction product of a nitrogenous baseneutralized with a neutralizing acid selected from anhydrides, organicacids, and inorganic acids.

In another embodiment, this invention provides an antimicrobial handwash comprising a soap; an antimicrobial agent; and the reaction productof monoethanolamine neutralized with lactic acid.

In a process in accordance with this invention, an antimicrobial handwash is produced. Soap is produced through the saponification of aprimary fatty acid with a primary nitrogenous base, wherein the mole tomole ratio for alkalinity of the primary nitrogenous base to freeprimary fatty acid is from about 1.5:1 to 3:1 such that there exists anexcess of primary nitrogenous base after the saponification. The excessprimary nitrogenous base is reacted with a secondary acid added to thesoap produced as above, the secondary acid being selected from the groupconsisting of carboxylic acids, organic acid anhydrides and mixed acidanhydrides to create an amine salt.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a hypothesized reaction between lactic acid andmonoethanolamine, in accordance with an embodiment of this inventionreduced to practice; and

FIG. 2 is a titration curve for monoethanolamine-lactic acidneutralization that experimentally verifies the correctness of theequation derived herein below respecting such neutralization.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The hand wash herein includes a soap; an antimicrobial agent; and anamine salt. The soap is made through a saponification reaction between aprimary fatty acid and a primary base. The amine salt is created throughthe neutralization of a nitrogenous base with a secondary acid.

The primary base may be a hydroxide; a nitrogenous base; an oxide of agroup I element, calcium, strontium, or barium; or the conjugate base ofa weak acid. As will be seen herein, the selection of the primary basecan affect the process methods that can be practiced to produce the handwash. With nitrogenous bases, the amine salt may be created either byneutralizing excess primary nitrogenous base left over after completionof the saponification reaction, in which case it is present in the soap,at creation, or by neutralizing the same primary nitrogenous base or adifferent secondary nitrogenous base in a separate process, in whichcase it is subsequently added to the soap created in the saponificationreaction. If the primary base is chosen to be a hydroxide; an oxide ofGroup I, calcium, strontium, or barium; or the conjugate base of a weakacid, the amine salt cannot be created by neutralizing an excess of thatbase, and a secondary nitrogenous base is neutralized to create theamine salt.

A secondary acid is employed to neutralize the excess nitrogenous baseor secondary nitrogenous base as the case may be. Thus, as alreadystated, “primary” relates to those acids and bases employed in thesaponification reaction, while “secondary” relates to those acids andbases employed to create the amine salt, although, when a nitrogenousbase is employed, it can serve as both the primary and the secondarybase. The amine salt created via the acid-base neutralization betweenthe secondary acid and either an excess primary nitrogenous base or asecondary nitrogenous base is found to have surprising antimicrobialproperties when combined with an antibacterial agent.

The soap is made from a primary fatty acid and a primary base. Theprimary fatty acid may be derived from crude fats or selected carboxylicacids, although it is typically less desirable to employ the crude fats.The crude fats include known animal fats, vegetable oils and the like,and generally have a glycerol linked with at least 1, but no greaterthan three fatty acids. The carboxylic acids, which are more preferred,may be selected from carboxylic acids having from 6 to 40 carbon atomsin the main fatty chain. In other embodiments, the carboxylic acids arechosen to have from 6 to 20 carbon atoms in the main fatty chain.

Suitable carboxylic acids include, and are not limited to, arachidicacid, arachidonic acid, beeswax acid, behenic acid, coconut acid, cornacid, cottonseed acid, erucic acid, hydrogenated coconut acid,hydrogenated menhaden acid, hydrogenated palm acid, hydrogenated tallowacid, hydroxystearic acid, isomerized linoleic acid, isomerizedsafflower acid, isostearic acid, lauric acid, linoleic acid, myristicacid, oleic acid, olive acid, palm acid, palmitic acid, palm kernelacid, peanut acid, pelargonic acid, rapeseed acid, rice bran acid,ricinoleic acid, safflower acid, soy acid, stearic acid, sunflower seedacid, tall oil acid, tallow acid, undecanoic acid, undecylenic acid, andwheat germ acid. Mixtures of the forgoing might also be employed. Inparticular embodiments, lauric acid is preferred.

Various primary bases can be selected for the saponification reaction,including hydroxides, nitrogenous bases, oxides of Group I, Ca, Sr, orBa, and conjugate bases of weak acids. A nitrogenous base is ultimatelyemployed to create the desired amine salt component of the hand wash,and thus if a nitrogenous base is not employed as the primary base forthe saponfication reaction, one must be employed as a secondary base tocreate the amine salt. If a nitrogenous base is used as the primarybase, the amine salt can be formed directly in the soap solution. Moreparticularly, an excess of nitrogenous base can be used in thesaponification reaction, and, once that reaction is complete, the excesscan be neutralized by a secondary acid to create the amine salt in situ.The processes for creating the hand wash are disclosed more fully below.

The nitrogenous base, whether primary or secondary, can be selected fromammonia and virtually any hydroxylated nitrogenous base. Suitablenitrogenous bases include, but are not limited to, 2-aminobutanol,aminoethyl propanediol, aminomethyl propanol, aminopropanediol,bis-hydroxyethyl tromethamine, butyl diethanolamine, butylethanolamine,dibutyl dthanolamine, diethanolamine, diisopropanolamine,diisopropylamine, dimethyl isopropanolamine, monoethanolamine, dimethylmonoethanolamine, ethyl ethanolamine, isopropanolamine, isopropylamine,methylethanolamine, methylglucamine, morpholine, triethanolamine,triispropanolamine, tromethamine. Mixtures of the forgoing might also beemployed. In particular embodiments, monoethanolamine is preferred.

The other primary bases suitable for use include hydroxides such ascalcium hydroxide, lithium hydroxide, potassium hydroxide, and sodiumhydroxide; metal oxides such as calcium oxide, and sodium oxide; andconjugate bases of weak acids such as dipotassium phosphate, disodiumphosphate, magnesium carbonate, pentapotassium triphosphate, petnasodiumtrisphosphate, potassium carbonate, sodium carbonate, tetrapotassiumpyrophosphate, tetrasodium pyrophosphate, and trisodium phosphate. Ifone or more of these other primary bases is employed as the primarybase, and there is not sufficient excess nitrogenous base (if any)employed, the nitrogenous base is to be employed as a secondary base.

The secondary acid used to neutralize either an excess of nitrogenousbase or a secondary nitrogenous base may generally be selected from theacid classes of anhydrides and organic and inorganic acids. Appropriateorganic compounds include, but are not limited to, carboxylic acids,organic acid anhydrides and mixed acid anhydrides. A non-exhaustive listof useful secondary acids as neutralizing agents includes linearcarboxylic acids such as acetic acid, lactic acid, and glycolic acid;homocyclic carboxylic acids such as acetylsalicylic acid; hetrocycliccarboxylic acids such as nicotinic acid; aromatic carboxylic acids suchas benzoic acid; branched aliphatic carboxylic acids such asisopropanoic acid; polyprotic carboxylic acids such as oxalic acid andsuccinic acid; and organic and mixed anhydrides such as benzoic acidanhydride and mixed phosphoanhydride. Suitable inorganic acids mayinclude, but are not limited to, strong and weak polyprotic acids suchas sulfuric acid and phosphoric acid; monoprotic weak acids such assodium bisulfate; monoprotic strong acids such as hydrogen halides andperchloric acid; and inorganic acid anhydrides such as carbon dioxide.In particular embodiments, lactic acid is most preferred.

The antimicrobial hand wash contains at least one antimicrobial agent,which is generally appreciated as a term of art for those compounds thatproduce acceptable time-kill antimicrobial activity to be suitable forsanitizing. More specifically, the hand wash herein has efficaciousproperties against both Gram-positive and Gram-negative microorganisms.For purposes of this disclosure, the terms “antimicrobial agent” is tocover compositions that have greater than 2 log kill reduction on bothGram-negative bacteria, specifically Klebsiella pheumoniae, andGram-positive bacteria, specifically Staphylococcus aureus.

In particular embodiments, the antimicrobial agent of the hand wash isselected from the group consisting of bisguanidines, quaternary ammoniumcompounds, benzyl alcohols, trihalocarbanilides, iodine containingcompounds, and phenolic compounds. Mixtures of the forgoing might alsobe employed. In particular embodiments, phenolic compounds are employed.

The phenol-based antimicrobial agents useful in this invention areexemplified by the following compounds, and may be used alone or incombination:

(a) 2-Hydroxydiphenyl Compounds

wherein Y is chlorine or bromine, Z is SO₂H, NO₂, or C₁-C₄ alkyl, r is 0to 3, o is 0 to 3, p is 0 or 1, m is 0 or 1, and n is 0 or 1. Inpreferred embodiments, Y is chlorine or bromine, m is 0, n is 0 or 1, ois 1 or 2, r is 1 or 2, and p is 0. In especially preferred embodiments,Y is chlorine, m is 0, n is 0, o is 1, r is 2, and p is 0. Aparticularly useful 2-hydroxydiphenyl compound has the structure:

having the adopted name, triclosan, and available commercially under thetradename IRGASAN DP 100, from Ciba Specialty Chemicals Corp.,Greensboro, N.C. Another useful 2-hydroxydiphenyl compound is2,2′-dihydroxy-5,5′-dibromodiphenyl ether. Additional bisphenoliccompounds are disclosed in U.S. Pat. No. 6,113,933, incorporated hereinby reference.(b) Phenol Derivatives

wherein R₁ is hydro, hydroxy, C₁-C₄ alkyl, chloro, nitro, phenyl, orbenzyl; R₂ is hydro, hydroxy, C₁-C₆ alkyl, or halo; R₃ is hydro, C₁-C₆alkyl, hydroxy, chloro, nitro, or a sulfur in the form of an alkalimetal salt or ammonium salt; R.sub.4 is hydro or methyl; and R₅ is hydroor nitro. Halo is bromo or, preferably, chloro.

Specific examples of phenol derivatives include, but are not limited to,chlorophenols (o-, m-, p-), 2,4-dichlorophenol, p-nitrophenol, picricacid, xylenol, p-chloro-m-xylenol, cresols (o-, m-, p-),p-chloro-m-cresol, pyrocatechol, resorcinol, 4-n-hexylresorcinol,pyrogallol, phloroglucin, carvacrol, thymol, p-chlorothymol,o-phenylphenol, o-benzylphenol, p-chloro-o-benzylphenol, phenol,4-ethylphenol, and 4-phenolsulfonic acid. Other phenol derivatives arelisted in WO 98/55096 and U.S. Pat. No. 6,113,933, incorporated hereinby reference.

(c) Diphenyl Compounds

wherein X is sulfur or a methylene group, R₁ and R′₁ are hydroxy, andR₂, R′₂, R₃, R′₃, R₄, R′₄, R₅, and R′₅, independent of one another, arehydro or halo. Specific, nonlimiting examples of diphenyl compounds arehexachlorophene, tetrachlorophene, dichlorophene,2,3-dihydroxy-5,5′-dichlorodiphenyl sulfide, 2,2′-dihydroxy-3,3′,5,5′-tetrachlorodiphenyl sulfide,2,2′-dihydroxy-3,5′,5,5′,6,6′-hexachlorodiphenyl sulfide, and3,3′-dibromo-5,5′-dichloro-2,2′-dihydroxydiphenylamine. Other diphenylcompounds are listed in WO 98/55096, incorporated herein by reference.

In particular embodiments, the phenol-based antimicrobial agent isselected from triclosan, 2,2′-dihydroxy-5,5′-dibromodiphenyl ether,pcmx, ortho-phenylphenol, and mixtures thereof.

As known, additional compounds are typically used to produce anacceptable hand wash for consumer use. These compounds include, but arenot limited to, foam modifying agents, pH adjusting agents, emollients,humectants, skin conditioning agents, dyes and fragrances. Herein, theymay be employed in amounts and for reasons known in the prior art.

There are two processes by which the hand wash of this invention mightbe created. In accordance with a process that is described herein as“super basing,” the saponification reaction between the primarynitrogenous base and the primary fatty acid is carried out in an aqueoussolution with an excess of primary nitrogenous base. Although it isnormal for saponification reactions to be carried out with an excess ofbase present, this invention adds to this general practice by creatingan amine salt from the excess base in situ. After the saponification iscomplete, excess base is backtitrated with the secondary acid to createthe amine salt directly within the soap solution. In accordance with aprocess that is described herein as “equivalent saponification,” thesaponification reaction is carried out with near equivalence of primarynitrogenous base and primary fatty acid, such that there is not asignificant excess of the primary base present after saponification. Theamine salt is added to the soap solution rather than being createdtherein, as in the super dosing process.

In the super dosing process, which employs a primary nitrogenous baseand a primary fatty acid in the saponification reaction, the mole tomole ratio for alkalinity to free fatty acid is preferably from about1.5:1 to 3:1, as opposed to the 0.8:1 to 1.25:1 ratios generallypracticed in saponification reactions. After completion of thesaponification, the excess nitrogenous base is backtitrated with asecond acid to an alkalinity to total acid ratio from about 0.8:1 to1.25:1, wherein “total acid ratio” takes into account the number ofmoles of both the primary fatty acid employed in the saponificationreaction and the secondary acid employed to create the amine salt. Theseratios are preferred only. It should be appreciated that the amine saltcould be produced to be present in virtually any amount, although thedisclosed ratios are preferred due to cost considerations.

In the equivalent saponification process, the mole to mole ratio foralkalinity to free fatty acid is substantially 1:1, such that there isan insubstantial amount of excess base at the completion of thesaponification reaction. This process is most likely used when theprimary base employed is not a nitrogenous base, and thus cannotcontribute to provide the amine salt in situ as in the super dosingprocess. The amine salt can either be created in a separate process, oreven purchased, and added to the soap solution, or it can be created byadding a secondary nitrogenous base to the soap solution and thereafterneutralizing it with a secondary acid. Although, again, the amine saltcould be added to be present in virtually any amount, it is preferableadded to comprise up to about 20% of the final hand wash formula, byweight.

For either saponification technique the pH of the solution should besimilar. The preferred pH is between 7 and 10.5.

The invention goes against common day teachings by using a large amountof excess base, and then the excess base is titrated with a second acidto an alkalinity to total acid ratio from about 0.8:1 to 1.25:1. Normalsaponification processes occur at alkalinity to fatty acid ratio fromabout 0.8:1 to 1.25:1.

If the antimicrobial agent has a limited solubility in water, as is thecase, for example, with phenol derivative antimicrobial agents, theantimicrobial agent is added to the soap solution as part of an “activepremix,” which is a solution of the antimicrobial agent dissolved in ahydric solvent. The hydric solvent should be chosen from eithermonohydric solvents, such as alcohols, or polyhydric solvents, such asglycols. The most preferred compounds are short carbon chain polyhydriccompounds, on the order of eight or less carbons, but longer chains canbe used. The sole use of the solvent is to dissolve the antimicrobialagent; it is therefore pertinent that the solvent have the ability toreadily dissolve the desired antimicrobial agent or agents. Theantimicrobial agent, whether in a premix or alone, may be added anytimeafter the completion of the saponification reaction. In accordance withparticular embodiments, the antimicrobial agent comprises from about0.01 to 10 wt % of the final formula; in other embodiments, from 0.05 to7.5 wt %; and in yet other embodiments, from 0.1 to 1 wt %.

The hand wash formulations of this invention are typically comprised offrom about 0.01 to 17.5 weight percent (wt %) of the primary fatty acid;from about 0.005 to 25 wt % of the primary base; and from about 0.01 to10 wt % of the antimicrobial agent. In particular embodiments, theprimary fatty acid comprises from about 0.05 to 17.5 wt % of the finalformula, and in yet other embodiments, from about 0.1 to 15 wt %. Inparticular embodiments, the primary nitrogenous base comprises fromabout 0.025 to 25 wt % of the final formula; in other embodiments, fromabout 0.05 to 22 wt %. The secondary base, whether it is the same as theprimary base or not, can be identified as any amount of base thatexceeds that needed for equivalent saponfication. The secondary base isfrom about 0.005 to 22.5 wt %, in yet other embodiments, from about0.025 to 22.5 wt %, and more particular from about 0.05 to 20 wt %. Thesecondary acid comprises from about 0.008 to 25 wt %, in yet otherembodiments from about 0.04 to 25 wt %, and more particular from about0.09 to 22.5 wt % of the hand wash formula.

In accordance with a particular embodiment reduced to practice,monoethanolamine is both the primary and secondary base, and it isreacted with lactic acid as the secondary acid to produce an amine salt,believed to be monoethanolammonium lactate. FIG. 1 shows the chemicalreaction. As pictured the acid and base react in a one mole to one moleratio. Lactic acid is a monoprotic acid, and this proton is the onetransferred during this reaction, creating a carboxylate anion. Theamine group found in monoethanolamine accepts the proton from the lacticacid via the lone pair of electrons on the nitrogen. This proton thencreates an ammonium cation.

The reaction occurs spontaneously, and there is one distinctcharacteristic of the reactants that determine the quality of thisreaction that need to be examined. First, the reaction generates heatand the temperature needs to be monitored because of detrimental effectsat high temperatures. With higher temperature, the oxidation ofmonoethanolamine via the loss of the amine group is expedited. Thereaction should be carried out slowly so the heat generated candissipate and not degrade the monoethanolamine. This can be a concernwith other nitrogenous bases, and should be taken into account to avoidnegatively impacting the reaction.

For the generation of just the amine salt, the pH is determined by acomplex equilibrium between both the weak conjugate base and weakconjugate acid of the product. Monoethanolammonium will donate theproton picked up from the lactic acid to water. Also, the absorption ofa proton via the negative portion of lactic acid occurs. The derivationof the equation to calculate the pH based on the acid and base used tocreate the salt is shown below:

B represents monoethanolamine and A represents lactate

Beginning with the conjugate acid dissociation:BH⁺+OH⁻

B+H₂O[B]/([OH⁻]*[BH⁺]) 1/K_(b)  1.Consider the disassociation of water:H₂O+H₂O

OH⁻+H₃O⁺[OH⁻]*[H₃O⁺]K_(w)  2.Combine equation 1 and 2:BH⁺+2H₂O+OH⁻

B+OH⁻+H₃O⁺+H₂O[OH⁻]*[H₃O⁺]*([B]/[OH⁻]*[BH⁺]) K_(w)/K_(b)  3.The like terms cancel leaving:BH⁺+H₂O

B+H₃O⁺([H₃O⁺]*[B])/[BH⁺]K_(w)/K_(b)  4.Now consider the disassociation of the acid:HA+H₂O

A⁻+H₃O⁺([A⁻]*[H₃O⁺])/[HA]K_(a)  5.Combine equations 4 and 5:BH⁺+2H₂O⁺HA

B+A⁻+2H₃O⁺([A⁻]*[H₃O⁺])/[HA]*([H₃O⁺]*[B])/[BH⁺]K_(w)*K_(a)/K_(b)  6.[A−] is equal to [BH+] at the equivalence point and assert that [HA] isequal to [B]BH⁺+2H₂O+HA

B+A⁻+2H₃O⁺[H₃O⁺]*[H₃O⁺]K_(w)*K_(a)/K_(b)  7.Manipulate the equation to produce the pH of the solution:BH⁺+2H₂O⁺ HA

B+A ⁻+2H₃O⁺ pH=−log(sqrt(K_(w)*K_(a)/K_(b)))  8.

Per the preferred embodiments, lactic acid, pK_(a) of 3.86, andmonoethanolamine, pK_(b) of 4.56, the pH at the equivalence point shouldbe 6.65. This is experimentally verified in FIG. 2. Because of thespontaneity of the reaction the ratio of acid to base can be in anyproportion, although near equivalence is most desired.

The resulting solution varies slightly in appearance depending on thereaction conditions. If the reaction is carried out slowly and the heatis allowed to dissipate the solution can be colorless, but if thereaction is done quickly and heat builds up, then the solution will turnto an amber color because of the oxidation of monoethanolamine. Thesolution also has a slightly honey-like odor. One inherent observationis an increase in the viscosity of the solution. Starting from two waterthin liquids, the final solution has a viscosity of about 1500 to 3000centipoise.

Although there are numerous antimicrobial agents, the most preferredembodiment contains halogenated diphenylether. Most specifically, theuse of pcmx and/or triclosan is most desired. These two compounds, andmost specifically triclosan, interact with the amine salt to produce amore efficacious hand wash. The hypothesis governing this trend isdescribed as charge interaction between the negatively charged triclosansubstitutents, chlorines and the hydroxyl group, and the positive chargefound on the amine group. Triclosan has a pK_(a) value of 7.4, so, atthe desired pH of the hand wash, the triclosan will be disassociated andhave a negative charge. The positive charge on the amine is attracted tothe negative charge on the triclosan and, thus, the triclosan ischelated and prevented from precipitating.

The antimicrobial properties of the hand wash containing an amine saltare improved compared to hand washes without. This improvement is seenboth in the broad spectrum inhibition and the quick inhibition. A logreduction of 2 on hard to kill organisms, specifically Staphylococcusaureus (MRSA) (ATCC# 33591) at 30 second exposure time, is desired and,as such, this hand wash provides greater than 2 log reduction of boththe Gram positive Staphylococcus aureus (MRSA) (ATCC# 33591) andShigella dysenteriae (ATCC# 13313).

EXPERIMENTAL Example 1

While making soap through a saponification reaction of a primarynitrogenous base with a primary fatty acid, the addition of excess basewas examined. Because the high pH resulting from excess base would beirritating and detrimental to the skin care properties of the hand wash,the excess base was neutralized with a second water soluble acid. For afirst control (Control 1), a hand wash made without excess base wastested along side the hand wash containing excess base neutralized withthe second acid. A second control (Control 2) excess base is present,but is not subsequently neutralized with the second acid. The handwashes included antimicrobial agent, namely triclosan. The base wasmonoethanolamine. The first acid was lauric acid, and the second waslactic acid.

The triclosan was dissolved in dipropylene glycol, to make an “activepremix.” The monoethanolamine was added to the water and then the lauricacid was added. After allowing the saponification process to complete,lactic acid was added to neutralize the excess base, and was added untilthe solution was brought to a pH of 9.25. The active premix was thenadded to the solution to create the antimicrobial hand wash. Theingredient amounts were as follows:

Excess Base: Control 1 Control 2: Water q.s. to 100 g q.s. to 100 g q.s.to 100 g Lauric Acid 5 g 5 g 5 g Monoethanolamine 3.833 g 1.7 g 3.833 gLactic Acid q.s. to pH 9.25 N/A N/A Dipropylene Glycol 3 g 3 g 3 gTriclosan 0.3 g 0.3 g 0.3 g pH: 9.22 pH: 9.21 pH: 10.30A log reduction test was performed for each formulation. The sampleswere tested by placing a loopful (approx 10 microliters) of theformulation into a microbial broth (Staph. Aureus ATCC# 6538) for 15seconds. A sample was then taken from the broth and plated. The bacteriawas grown and then counted resulting in a quantitative reduction value,as shown below.

-   Control 1: log reduction 0.6-   Excess Base: log reduction 4.0-   Control 2: log reduction 1.3

There is a dramatic increase in the log reduction for the antimicrobialhand wash employing excess base subsequently neutralized with a secondacid. This suggests that the neutralized excess base improves theantimicrobial properties of the hand wash.

Example 2

Because there is a boost in the efficacy of the product due to the useof excess primary nitrogenous base and a secondary neutralizing acid,alternate bases were tested. The focus was to find suitable weaker basesthat might be used, because weaker bases should further reduce thedegree of skin irritation experienced when using a resultantantimicrobial hand wash. Samples were made using the same procedure asin Example 1, but with alternate bases. Because the bases had differentmolecular masses, the percentage used in each sample was different. Thiswas done in order to ensure that the same number of moles were presentin each sample, thus allowing for the same concentration of amine saltin the final hand wash. As mentioned the same formulation was used as inExample 1, but with the base, monoethanolamine, replaced with thefollowing:

Alternate Bases

Triethanolamine 9.355 g Equistar, USA Aminomethylpropanol (AMP-95) 5.525g ANGUS Chemical, USA Tetrahydroxypropyl 10.29 g BASF, USAethylenediamine (Neutrol TE)Log reductions were calculated as follows:

Triethanolamine hand wash 4.1 AMP-95 hand wash 1.4 Neutrol TE hand wash1.7

Despite having better skin compatibility due to the fact that theyemploy weaker bases, the log reductions for these antimicrobial handwashes were not as high as that for the monoethanolamine-basedantimicrobial hand wash of Example 1.

Example 3

In this example, alternate acids were considered for use in neutralizingexcess base present after the saponification reaction, i.e, to replacethe lactic acid specifically used in Example 1. The samples were made inaccordance with Example 1, except that the lactic acid was replaced withalternate acids. A sample was also created having excess base and nosecond acid addition. The samples were adjusted to pH: 9.2+/−0.10 witheach acid, and then tested for log reduction properties. The acidstested were as follows:

Acid Amount pH Log Reduction None N/A 10.15 1.6 Hydrochloric acid 47.66g 9.19 3.1 Phosphoric acid 1.52 g 9.17 3.5 Sulfuric acid 12.20 g 9.183.4 Ascorbic acid 4.68 g 9.17 4.4 Malic acid* 1.87 g 9.12 2.8 Succinicacid 1.75 g 9.17 2.8 Glycolic acid 2.04 g 9.16 3.0 Acetic acid 43.68 g9.19 2.2

From the high pH sample, it is plain to see the amine salt is importantfor the efficacious properties of the hand wash. Of the different acidstested, all drastically improved the log reduction values for the handwash. The hydrochloric, sulfuric, and acetic acid required large amountsof acid because the two solutions were dilute compared to the otheracids (either concentrated in solution or crystals).

Experiment 4

In this example, tests were run to determine whether the baseneutralized with the second amine acid (i.e., the amine salt) must becreated in the hand wash from excess base left over from an initialsaponification reaction or if it could be added as a separate additionto a soap solution produced without excess base. Monoethanolamine andlactic acid were neutralized in water in a separate “neutralizationsolution,” i.e., the monoethanolamine is not present as excess in asaponfication reaction. The neutralization solution was made as follows:

122.34 g  Water 45.81 g Monoethanolamine 76.90 g Lactic acid

The monoethanolamine was dissolved in the water, and the lactic acid wasslowly added to the solution, because, if added too quickly, the heatnot dissipated from the neutralization reaction would degrade themonoethanolamine. The degradation can be seen by a color change from aclear colorless mixture to a dark amber hue. A hand wash was made perExample 1 procedures, but without excess base (monoethanolamine). Thesolution was then split into four separate solutions so that theneutralization solution could be added in differing amounts.

Hand Wash Formula Water q.s. to 100 g Lauric Acid 5 g Monoethanolamine1.7 g Dipropylene Glycol 3 g Tricloan 0.3 g Neutralization solution SeeTable below. Amount Amount Neutralization Amount Log Sample Formulasolution water Reduction A 87.2 g 12.8 g 0 g 4.7 B 87.2 g 6.4 g 6.4 g3.7 C 87.2 g 3.2 g 8.6 g 3.1 D 87.2 g 0 g 12.8 g 2.1

The amount of monoethanolammonium lactate is directly proportional tothe log reduction.

Experiment 5

The hand wash here is a preferred hand wash containing optionalingredients that are generally appreciated for their beneficialproperties in hand wash formulations. The production process involvesdissolving pcmx in dipropylene glycol, saponifying the lauric acid withmonoethanolamine, and adding the remaining ingredients to the water.

Chemical Amount Supplier Water q.s. to 100 g — Ethyl Alcohol 10 g GrainProcessing Corp., USA Lauric Acid 5 g Proctor & Gamble, USAMonoethanolamine 3.833 g Equistar Chemicals, USA Dipropylene Glycol 3 gHuntsman, USA Lactic Acid 90% USP 2.733 g Purac, USA Polozamer 124 1 gBASF, USA PCMX 0.505 g Netchem Inc, Canada Versene 100 0.5 g BASF, USAMethyl Paraben 0.3 g RITA Corp., USA Propyl Paraben 0.3 g RITA Corp.,USA Sodium Metabisulfite 0.1 g Esseco General Chemistry, USA

The sample was then inoculated into samples containing a microorganismin duplicate. One of the two samples was neutralized at 15 seconds andthe second at 30 seconds. The samples were then plated and incubated forlater counting. The data are represented below.

ATCC Log₁₀ Percent Microorganism Num. Exposure Time Reduction ReductionAcinetobacter 19606 15 sec. 4.1775 99.9934 baumannii Campylobacter 2942815 sec. 5.0453 99.9991 jejuni Citrobacter 8090 15 sec. 4.1351 99.9927freundii Clostridium 13124 15 sec. 6.9345 99.9999 perfringensEnterococcus 51575 15 sec. 6.2822 99.9999 faecalis 30 sec. 6.282299.9999 Enterococcus 51559 15 sec. 5.8921 99.9999 faecium 30 sec. 5.892199.9999 Escherichia coli 11229 15 sec. 3.7889 99.9837 Escherichia coli43888 15 sec. 3.7520 99.9823 Klebsiella 13883 15 sec. 3.6385 99.9770pneumoniae Listeria 7644 15 sec. 6.5378 99.9999 monocytogenesPseudomonas 15442 15 sec. 3.7818 99.9235 aeruginosa Salmonella 13076 15sec. 4.0550 99.9912 choleraesuis Salmonella 14028 15 sec. 3.9138 99.9878cholerasius Shigella 13313 15 sec. 3.9217 99.9880 dysenteriae Shigellasonnei 11060 15 sec. 3.9004 99.9874 Staphylococcus 6538 15 sec. 6.064599.9999 aureus 30 sec. 6.0645 99.9999 Staphylococcus 33591 15 sec.1.9860 98.9672 aureus 30 sec. 2.3486 99.5519

The sample has broad spectrum, quick acting activity against these 17tested organism.

In light of the foregoing, it should thus be evident that the process ofthe present invention, providing an antimicrobial hand wash,substantially improves the art. While only the preferred embodiments ofthe present invention have been described in detail hereinabove, thepresent invention is not to be limited thereto or thereby. Rather, thescope of the invention shall include all modifications and variationsthat fall within the scope of the attached claims.

1. A process for producing an antimicrobial hand wash comprising thesteps of: producing a soap through the saponification of a primary fattyacid with a primary nitrogenous base, wherein the mole to mole ratio foralkalinity of the primary nitrogenous base to free primary fatty acid isfrom about 1.5:1 to 3:1 such that there exists an excess of primarynitrogenous base after the saponification; reacting the excess primarynitrogenous base with a secondary acid selected from the groupconsisting of carboxylic acids, organic acid anhydrides and mixed acidanhydrides to create an amine salt.
 2. The process of claim 1, whereinthe primary fatty acid is selected from the group consisting of fattyacids derived from crude fats and carboxylic acids having from 6 to 40carbon atoms in the main fatty chain.
 3. The process of claim 2, whereinsaid primary fatty acid is a carboxylic acid selected from the groupconsisting of arachidic acid, arachidonic acid, beeswax acid, behenicacid, capric acid, caproic acid, caprylic acid, C10-40 hydroxyalkylacid, C32-36 isoalkyl acid, coconut acid, corn acid, cottonseed acid,erucic acid, hydrogenated coconut acid, hydrogenated menhaden acid,hydrogenated palm acid, hydrogenated tallow acid, hydroxystearic acid,isomerized linoleic acid, isomerized safflower acid, isostearic acid,lauric acid, linoleic acid, myristic acid, oleic acid, olive acid, palmacid, palmitic acid, palm kernel acid, peanut acid, pelargonic acid,rapeseed acid, rice bran acid, ricinoleic acid, safflower acid, soyacid, stearic acid, sunflower seed acid, tall oil acid, tallow acid,undecanoic acid, undecylenic acid, and wheat germ acid.
 4. The processof claim 3, wherein said primary nitrogenous base is selected from2-aminobutanol, aminoethyl propanediol, aminomethyl propanol,aminopropanediol, bis-hydroxyethyl tromethamine, butyl diethanolamine,butylethanolamine, dibutyl dthanolamine, diethanolamine,diisopropanolamine, diisopropylamine, dimethyl isopropanolamine,monoethanolamine, dimethyl monoethanolamine, ethyl ethanolamine,isopropanolamine, isopropylamine, methylethanolamine, methylglucamine,morpholine, triethanolamine, triispropanolamine, tromethamine, andmixtures thereof.
 5. The process of claim 1, wherein said secondary acidis selected from the group consisting of acetic acid, lactic acid,glycolic acid, acetylsalicylic acid, nicotinic acid, benzoic acid,isopropanoic acid, oxalic acid, succinic acid, benzoic acid anhydride,mixed phosphoanhydride, and mixtures thereof.
 6. The process of claim 1,further comprising the steps of: dissolving a phenol-based antimicrobialagent in a hydric solvent to create an active premix; and mixing theactive premix with the soap.
 7. The process of claim 6, wherein saidphenol-based antimicrobial agent is selected from the group consistingof triclosan, 2,2′-dihydroxy-5,5′-dibromodiphenyl ether,p-chloro-m-xylenol, ortho-phenylphenol, and mixtures thereof.
 8. Theprocess of claim 7, wherein the primary nitrogenous base ismonoethanolamine, and the secondary acid is lactic acid.